Does lithium in vitro and ex vivo alter the release of [3H]noradrenaline from brain tissue and the sensitivity of presynaptic autoreceptors?
The effect of lithium on the release of noradrenaline (NA) was investigated in slices of the cerebral cortex and hippocampus from the rat in vitro and ex vivo. In vitro, small concentrations of lithium chloride (1 and 2 mM) failed to alter the electrically stimulated tritiated overflow from slices preincubated with [3H]NA. Larger concentrations of lithium chloride (5 and 10 mM) significantly increased the electrically evoked overflow of [3H]NA by 18-40% as well as the basal 3H efflux. The alpha 2-adrenoceptor agonist clonidine inhibited, whereas the alpha 2-adrenoceptor antagonist rauwolscine facilitated the stimulated overflow of [3H]NA. These effects were attenuated by 10 mM lithium chloride but not by 2 mM. In slices of brain obtained from rats treated for 5 weeks with lithium chloride, the electrically evoked release of [3H]NA, as well as the inhibition of release of [3H]NA, induced by the alpha 2-adrenoceptor agonist clonidine were unaltered. It is concluded that therapeutically relevant concentrations of lithium do not influence the release of NA and that the function of presynaptic alpha 2-autoreceptors is not affected by chronic treatment with lithium. The increase in release of [3H]NA by larger concentrations of lithium may be relevant to its toxic effects.
Gross
G
G
Institut für Pharmakologie, Universitätsklinikum Essen, Federal Republic of Germany.
Hanft
G
G
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000378:metabolism; D013569:Synapses / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D011941:Receptors, Adrenergic; D015016:Yohimbine; D008094:Lithium; D003000:Clonidine; D009638:Norepinephrine